Rosuvastatin, which is an antihypercholesterolemic drug, is chemically known as (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-methyl(methylsulfonyl)amino]pyrimidin-5-yl]-(3R,5S)-3,5-dihydroxyhept-6-enoic acid calcium (2:1) salt of formula II. Rosuvastatin was for the first time disclosed in U.S. Pat. No. 5,260,440. Rosuvastatin is being marketed under the proprietary name CRESTOR, as an oral tablet, for the treatment of hypercholesterolemia. In view of the importance of Rosuvastatin as a lipid-lowering agent, several synthetic methods have been reported in the literature to prepare rosuvastatin, some of which are summarized below:
U.S. Pat. No. 5,260,440 discloses a process for preparing Rosuvastatin in examples. The process is as shown below:

The difficulties in the above process are that the intermediate (A) is not obtained in pure form and its purification is tedious and overall yield is extremely low. Even, when intermediate (A) is not obtained in pure form, further condensation with intermediate (8) to form Rosuvastatin, which does not result in Rosuvastatin of right quality as the product contains unacceptable quantity of impurity levels.
WO 2000/049014 A1 describes a novel chemical process for the preparation of ter-butyl (E)-(6-{2-[4-(4-fluorophenyl)-6-isopropyl-2-methyl(methylsulfonyl)amino]-pyrimidin-5-yl]vinyl}-(4R,6S)-2,2-dimethyl[1,3]dioxan-4-yl)acetate, which comprises reacting diphenyl-{4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methyl-sulfonyl)amino]pyrimidin-5-ylmethyl}phosphineoxide with tert-butyl 2-[(4R,6S)-6-formyl-2,2-dimethyl-1,3-dioxan-4-yl]acetate and its further conversion to rosuvastatin.
WO 2003/097614 A2 describes a modified procedure for the preparation of the starting material 4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]-pyrimidin-5-carboxaldehyde and further conversion to rosuvastatin by condensing with methyl (3R)-3-[(ter-butyldimethylsilyl)oxy]-5-oxo-6-triphenylphosphoranylidene hexanoate. The condensed product was deprotected using methanesulfonic acid and subsequently converted to Rosuvastatin calcium (2:1) salt.
WO 2004/014872 A1 describes a process for the manufacture of Rosuvastatin calcium (2:1) salt, which comprises mixing a solution of calcium chloride with a solution of water soluble salt of (E)-7-[4-(4-fluorphenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl]-(3R,5S)-3,5-dihydroxy-hept-6-enoic acid. This process for the preparation of Rosuvastatin employs the use of phosphorane side chain, the preparation of side chain requires eight synthetic steps and involves expensive reagents. This process is uneconomical and time consuming, hence not appropriate for commercial scale operation.
WO 2006/100689 A1 discloses a process for preparation of Rosuvastatin, which is as shown below:

In the above scheme, R1, R2, R3 represents substituted or unsubstituted phenyl and R4 represents an aliphatic residue selected from C1-4 alkyl; R5 represents C1-4 alkyl which is optionally substituted by hydroxyl; R6 represents hydrogen, halogen, C1-4 alkyl or C1-4 alkoxy; R7 represents aliphatic residue and R8 represents C1-4 alkyl.
WO 2006/106526 A1 describes the preparation of Rosuvastatin, which is as shown below:

In the above mentioned scheme, R1, R2, R3 are substituted or unsubstituted phenyl and R4 is an aliphatic residue selected from C1-4 alkyl; R5 represents C1-4 alkyl, M is an alkali metal salt. X represents a halogen; R6 represents C1-4 alkyl, which is optionally substituted by hydroxyl; R7 represents hydrogen, halogen, C1-4 alkyl or C1-4 alkoxy; R8 is an aliphatic residue selected from C1-4 alkyl.
WO 2006/076845 A1 describes a process to prepare Rosuvastatin and its salt thereof, which is as shown below:

We have now found an improved process to prepare (2E)-3-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonylamino)pyrimidin-5-yl]propenal of Formula I and subsequently converting the compound of Formula I to Rosuvastatin and its pharmaceutically acceptable salts thereof of Formula II.
Objective
The main objective of the present invention is to provide an improved process for preparing (2E)-3-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonyl-amino)pyrimidin-5-yl]propenal, which is an useful intermediate in the preparation of Rosuvastatin.
Yet another objective of the present invention is to provide an improved process for preparing (2E)-3-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonyl-amino)pyrimidin-5-yl]propenal, which is simple, industrially applicable and economically viable.
Another objective of the present invention is to provide a process for a novel intermediate that is used in the preparation of rosuvastatin calcium.